10 The PON1 p.Q192R missense variant (c.575A>G, rs662) is the most extensively characterized PON1 SNP and has been associated with CAD susceptibility in numerous studies.
9 Furthermore, meta-analysis of clinical studies suggests a link between low levels of PON1 in serum and increased risk of CAD. 8 Conversely, overexpression of PON1 showed opposite results. 7 Previous studies on animal models have shown that transgenic PON1 knockout mice developed increased lipid oxidation and atherosclerosis. PON1 is a glycoprotein associated with serum high-density lipoprotein (HDL) and has a central role in metabolizing lipid peroxides, exhibiting antiatherogenic properties. 5, 6 Among the genetic factors, paraoxonase-1 (PON1) is one of the most studied risk factors. 4 Importantly, the complex interaction between these factors and genetic factors, including single-nucleotide polymorphisms (SNP), has taken a central role in understanding the pathophysiology of this disease and the extensive variability susceptibility observed in populations. 3 Non-genetic risk factors for atherosclerosis have been thoroughly described and are highly prevalent in the Latin-American population. Blood flow occlusion results in both acute and chronic conditions, such as stable angina, acute coronary syndrome (ACS) and chronic ischemic heart disease. 2 CAD is almost always due to atheromatous vessel narrowing and subsequent impaired blood flow to the heart. 1 In 2019, 8.9 million deaths were caused by this disease, representing a major burden on healthcare systems, especially in developing countries.
Keywords: PON1, genetic risk, cardiovascular disease susceptibility, platelet reactivity, clopidogrelĬoronary artery disease (CAD) is the most prevalent cardiovascular disease and the leading cause of mortality globally, accounting for 16% of deaths worldwide. We found no association between the polymorphism and HPR.Ĭonclusion: We propose that PON1 p.Q192R is a potentially useful marker for CAD susceptibility in the Colombian population and lacks association with HPR under clopidogrel treatment. The allele 192R was positively associated with decreased susceptibility to CAD under a dominant model (OR, 0.58 95% CI, 0.42– 0.8 P < 0.01). The allele distribution was found to be statistically different from the control group and other ethnic groups. Results: The allele frequencies for the PON1 192Q and 192R alleles were 0.60 and 0.40, respectively. We determined the association between PON1 p.Q192R polymorphism, increased susceptibility to CAD and high on-treatment platelet reactivity (HPR) by using odds ratio (OR) and 95% confidence interval (CI) on four genetic models. Response to clopidogrel was determined by assessing the platelet function using the INNOVANCE PFA-200 System. The allele frequencies for the PON1 192Q and 192R alleles were determined in cases and Latin-American controls obtained from the public database gnomAD (n = 17,711). Patients and Methods: The study was conducted among 163 patients diagnosed with CAD and treated with clopidogrel. Purpose: We aimed at investigating the association of PON1 p.Q192R with CAD and clopidogrel response in Colombian population. The polymorphism p.Q192R has been previously associated with coronary artery disease (CAD) susceptibility and clopidogrel response. *These authors contributed equally to this workĬorrespondence: Dora Janeth Fonseca MendozaĬenter for Research in Genetics and Genomics (CIGGUR), GENIUROS Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Cra 24 # 63C69, Bogotá, 112111, Colombiaīackground: Paraoxonase-1 (PON1), a glycoprotein associated with serum high-density lipoprotein (HDL), has a central role in metabolizing lipid peroxides, exhibiting antiatherogenic properties.
David Corredor-Orlandelli, 1, * Santiago Sambracos-Parrado, 1, * Santiago Mantilla-García, 1 Josué Tovar-Tirado, 1 Valentina Vega-Ramírez, 1 Santiago David Mendoza-Ayús, 1 Laura Catalina Peña, 1 María Fernanda Leal, 1 Juliana Rodríguez-Carrillo, 1 Juanita León-Torres, 1 Juan Mauricio Pardo-Oviedo, 2 Katherine Parra Abaunza, 3 Nora Contreras Contreras Bravo, 1 Oscar Ortega-Recalde, 1 Dora Janeth Fonseca Mendoza 1ġCenter for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia 2School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia 3Hospital Universitario Mayor – Méderi, Universidad del Rosario, Bogotá, Colombia